The present invention relates generally to the field of viral proteins, and more specifically to vital proteins having immunoregulatory activity.
The immune system protects an organism from infection and disease through the interaction of specialized white blood cells which recognize and destroy invading microbes and diseased cells. The specialized white blood cells are controlled and coordinated by specific proteins known as cytokines, which direct the development, proliferation, function and effectiveness of these cells. Cytokines act upon immune cells by binding specific proteins, called cytokine receptors, which are located on immune cell surfaces.
The immune response can be modulated by cytokine antagonists, which act by binding cytokines, and preventing the cytokines from binding their respective receptors. Pathogenic organisms may make use of such cytokine antagonists to modulate an infected organism's immune response. Certain viruses are exemplary of such pathogens; the genetic material of such viruses encodes proteins which are similar to certain mammalian cytokine receptors, and which bind to a cytokine and prevent that cytokine from exerting an effect upon an immune cell.
Poxviruses are large, structurally-complex, DNA-containing viruses. Within the Poxviridae family, the subfamily Chordopoxvirinae comprises six genera of poxviruses, including Othopoxvirus, Leporipoxvirus and Avipoxvirus. Vaccinia virus (VV), an Orthopoxvirus, is considered the prototypic poxvirus; significant strides have been made in understanding the molecular biology of poxviruses by studying VV (reviewed in P. Traktman, Cell 62:621-626; 1990).
The entire sequence of the Copenhagen strain of vaccinia virus has been published (Paoletti et al., Virology 179:247-266, 1990). The Copenhagen sequence predicts 198 open reading frames (ORFs) of at least 60 amino acids. Howard et al. (Virology 180:633-647; 1990) report the structure of nine ORFs from the right-hand inverted terminal repeat (ITR) of the WR strain of vaccinia virus. Very few ORFs have been identified as encoding specific viral proteins.
The present invention identifies a specific class of poxvirus proteins having immunosuppressive activity, and provides a method for identifying and isolating such viral proteins. The invention also provides pharmaceutical compositions for regulating immune responses.